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Approcci di intervento delle neuroscienze cliniche e della neuropsichiatria alle new e old addictions Workshop Internazionale Nuove metodiche di intervento in ambito neuropsichiatrico e neuroscientifico Maria Cotelli IRCCS Fatebenefratelli - Brescia Brescia, 8 Aprile 2017 Neuroscienze sociali e addiction Experimental neuropsychology and social neuroscience approaches provide the opportunity to better describe and understand the interplay between social functioning and the development of addiction. . Yücel et al 2017 Le neuroscienze sociali rappresentano un ambito di ricerca multidisciplinare che integra dati provenienti da tre differenti livelli di analisi: - Sociale - Cognitivo - Neurale Ochsner and Lieberman, 2001 Cognizione sociale È l’insieme delle capacità che permettono ad un individuo di costruire rappresentazioni mentali delle relazioni esistenti tra se stesso e gli altri e di utilizzare queste informazioni per muoversi efficacemente nel proprio mondo sociale The social brain Adolphs, 1999 Neuroscience tools Neurofeedback Neurostimulation and neuromodulation Virtual reality Social cognition/rTMS e tDCS Tecniche non invasive di stimolazione hanno confermato la presenza di un sistema neurale distribuito sottostante ai compiti di cognizione sociale Historical background Plasticità cerebrale Egyptian tomb dating 2 500 BC, showing small boat with a man who has hooked a Nile catfish and is going to experience a painful shock Historical background Plasticità cerebrale In 43-48 a.c. Scribonio Largo (1529) observed that placing a live torpedo fish - delivering a strong direct electric current – over the scalp of a patient with headache elicited a sudden, transient stupor with pain relief. Priori, 2003 Historical background Plasticità cerebrale Luigi Galvani Alessandro Volta Draft of Voltas’s letter to Banks, announcing the invention of the battery 1799-1800 Piccolino, 1998 The prepared frog and the electric machine, 1791 Historical background Plasticità cerebrale Giovanni Aldini Galvani’s nephew, Giovanni Aldini, in 1804 reported the successful treatment of patients suffering from melancholia by applying galvanic currents over the head. Parent, 2004; Priori, 2003 Repetitive Transcranial Magnetic Stimulation Introduzione rTMS Transcranial magnetic stimulation (TMS) has provided over two decades of data in focal, non-invasive brain stimulation based on the principles of electromagnetic induction. TMS is a neurostimulation and neuromodulation technique rTMS: Meccanismi di azione In general, “high-frequency stimulation” refers to frequencies above ≥5Hz and is considered to produce an excitatory effect, whereas “low frequency stimulation” refers to frequencies below ≤1Hz causing inhibition of cortical excitability. Chen et al., 1997; Fregni and Pascual-Leone, 2007 Polarity-dependent excitability-modulation during tDCS Plasticità cerebrale 1.5 kS MEP-Amplitude with/without tDCS * prm 1.25 m pom * 1.0 anodal stimulation oc Weak tDCS (1÷ 2mA) with a homogenous positions: currentElectrode field modulate brain excitability via polarization m =membrana motor cortex; prm = premotor 0.75 m-cS 0.5 cm cathodal stimulation cortex; pom = post-motor cortex; oc occipital; cS = contralateral tDCS= is a neuromodulation technique forehead; cm = kontralateral motor cortex Nitsche & Paulus, 2000 transcranial Direct Current Stimulation (tDCS) Plasticità cerebrale 5 minutes of Anodal or Cathodal tDCS (1mA) modify MEPs amplitude Nitsche and Paulus, 2000; 2001; Wassermann and Grafman, 2005 tDCS vs TMS tDCS Neuromodulation • Very inexpensive and portable • Sham Stimulation: comparable perceptual feelings • Spatial resolution of stimulation: tDCS has poor spatial resolution • tDCS is ideal for online protocols • Believed to be exceptionally safe • Does not induce action potentials in axons • Believed to modulate the firing rate of active neurons • Depending on polarity, tDCS can induce cortical excitability reduction or enhancement that can persists for hours or days TMS Neuromodulation, Neurostimulation • Relatively expensive • Sham Stimulation: Sham coil • Spatial resolution of TMS stimulation depends of coils size and configuration • Moderate side effects (e.g. mild speech arrest) • TMS is less ideal to be used during a training/task • Safe, but there are reports of inducing seizures when high amplitude and frequency are combined • TMS induces a current that can elicit action potentials in neurons; • Depending on frequency, sustained TMS can induce excitability reduction or enhancements that can persist for hours or days. Nitsche et al., 2008; Priori et al., 2009; Dayan et al., 2013; Woods et al., 2016 tDCS e Social Neuroscience • • Very inexpensive and portable; Sham Stimulation: comparable perceptual feelings; • tDCS is ideal for online protocol; • Believed to be exceptionally safe; • Depending on polarity, tDCS can induce cortical excitability reduction or enhancement that can persists for hours or days; Great potential of tDCS for brain stimulation studies investigating social interaction Knoch et al., 2008; Sellaro et al., 2016 tDCS clinical application on Addictions Substance use Disorders Behavioural Addictions The rationale of expanding tDCS work to addictions is justified by its positive effect on decision-making process (improved) and on risk- taking (reduced) Sauvaget et al., 2015 tDCS e addiction • Noninvasive brain stimulation, among which transcranial direct current stimulation(tDCS), has opened up new perspectives in addiction treatment. Rangel, Camerer & Montague (2008) Neurocircuitry of Addiction Goldstein and Volkow, 2002; Koob, Everitt and Robbins, 2008; Tang et al., 2015 Addiction e tDCS Bihemispheric stimulation of the DLPFC with the anode on right (F4) and cathode on the left (F3) hemisphere F4 - tDCS F3 + Lefaucheur et al 2017 Gambling Goldstein and Volkow, 2002; Koob, Everitt and Robbins, 2008; DiLeone et al 2009;Tang et al., 2015; Meng et al 2014 tDCS e Gambling . 36 young participants performed a gambling risk task while receiving: • Anodal tDCS over the right and cathodal tDCS over the left DLPFC • Anodal tDCS over the left and cathodal tDCS over the right DLPFC • Sham tDCS Fecteau et al., 2007 tDCS e Gambling When healthy participants (young) received anodal stimulation over the right DLPFC coupled with cathodal tDCS over the left DLPFC, they chose more often the safe prospects they diminish risk-taking Fecteau et al., 2007 tDCS e Gambling Participants receiving left anodal ⁄ right cathodal stimulation choose more often high-risk choices (contrary to previous findings in young subjects) Boggio et al., 2010 28 older adults performed a gambling risk task while receiving: • Anodal tDCS over the right and cathodal tDCS over the left DLPFC • Anodal tDCS over the left with cathodal tDCS over the right DLPFC • Sham tDCS tDCS e Gambling * Randomized double blind between subjects design • • • Cathodal over the right DLPFC increased IGT score Benussi et al., 2017 20 PD patients anodal 2mA over right DLPFC 20 PD patients cathodal 2mA over right DLPFC 20 PD patients placebo stimulation During IOWA Gambling Task (IGT) Global IGT score: difference between advantageous and disadvantageous choices Target areas and main findings of tDCS studies on social neuroscience Boggio et al., 2016 La Teoria della Mente è la capacità di attribuire a sé e agli altri stati mentali quali desideri, intenzioni, pensieri e credenze e di spiegare e prevedere i comportamenti sulla base di queste inferenze. Premack e Woodruff, 1978 La teoria della mente (ToM) permette di interpretare il proprio mondo sociale con la consapevolezza che le persone agiscono sulla base dei rispettivi contenuti mentali e viene utilizzata dal soggetto ogni qualvolta si trova a cercare di attribuire un significato al comportamento proprio e altrui ToM è un'abilità fondamentale per la vita sociale Brune and Brune-Cohrs. 2006 Teoria della mente e addiction Le abilità di ToM e di riconoscimento delle emozioni appaiono deficitarie in soggetti con diagnosi di Abuso e/o Dipendenza da alcol Bora e Nabi, 2016; Onuoha et al., 2016; Sanvicente-Vieira et al 2017 Correlati neurali della ToM Sistema neurale distribuito sottostante il meccanismo neurocognitivo della Teoria della Mente Amodio and Frith, 2006; Saxe and Powell, 2006; Carrington and Bailey, 2009 tDCS e ToM Due task: 1. Riconoscimento emozioni 2. Abilità di adottare la prospettiva dell’altro 16 Soggetti (8 maschi e 8 femmine) 1.0 mA biemisferica tDCS per 15 minuti Anodica Left/ catodica Right oppure Anodica R/catodica L - tDCS o sham I partecipanti eseguono compiti sperimentali dopo tDCS Conson et al., 2015 tDCS e ToM 1. Riconoscimento emozioni Esclusivamente nel gruppo dei partecipanti maschi si osserva riduzione dei RT per il riconoscimento dell’espressione facciale di paura dopo tDCS anodica destra e catodica sinistra. Nessun effetto nelle donne Conson et al., 2015 tDCS e ToM 2. Abilità di adottare la prospettiva dell’altro In tutti i soggetti (maschi e femmine) tDCS anodica destra e catodica sinistra riduce la capacità di adottare la prospettiva dell’altro (aumento tempi reazione e riduzione accuratezza) Conson et al., 2015 ToM e differenze di genere Frontotemporal Dementia ? Alzheimer’s Disease Theory of Mind e empathizing–systemizing theory According to empathizing–systemizing theory females are, on average, more disposed to an empathizing style— i.e., the drive to identify others’ mental states in order to predict their behavior and respond with an appropriate emotion. On the other hand, males are, on average, more disposed to a systematizing style, i.e., the drive to predict and to respond to the behavior of non-agentive deterministic systems by inferring the rules that govern such systems. Baron-Cohen, 2010 Neuroimaging, ToM e differenze di genere Nei maschi maggiore attivazione mPFC quando si fa credere che il partner di gioco è un uomo e non un computer partner Krach et al., 2009 Krach et al 2009 RME task Baron-Cohen et al., 2001 Serafin and Surian, 2004 Adenzato et al., 2017 tDCS and theory of mind EXP 1: 16 males & 16 females mPFC and placebo EXP 2: 16 females CZ and placebo Adenzato et al., 2017 tDCS and theory of mind Adenzato et al., 2017 Highlights Plasticità cerebrale • Experimental neuropsychology and social neuroscience approaches now provide the opportunity to better describe and understand the interplay between social functioning and the development of addiction. • tES techniques are considered well tolerated (where precise established protocols are followed) and operated by influencing neuronal activity, generating gradual changes in neural networks. • tDCS is an effective and relevant technique to be used in social neuroscience. • Studies on non-invasive brain stimulation with weak electrical currents have shown potential benefits by the induction of changes in cortical excitability and, consequently, in neuroplasticity. Highlights Plasticità cerebrale • To date, findings are encouraging, but sham-controlled studies are still insufficient to allow endorsement of widespred use of these techniques, despite the great margin of safety if appropriate guidelines and precautions are followed. • The effects of these techniques seem to depend on the parameters of the stimulation which explains the variability of the results. • While there is an increased understanding of the mechanisms of tDCS, the mechanisms that underline other tES methods are poorly understood. Grazie Unità di Ricerca in Neuroscienze sociali e delle emozioni Dipartimento di psicologia Università Cattolica del Sacro Cuore Centro di Scienza Cognitiva Dipartimento di Psicologia, Università degli studi di Torino Michela Balconi Davide Crivelli Francesca Pala Maria Elide Vanutelli Mauro Adenzato Ivan Enrici Clinica Neurologica, Università degli studi di Brescia Alessandro Padovani Barbara Borroni Alberto Benussi Unità di Neuropsicologia IRCCS Centro San Giovanni di Dio Fatebenefratelli Brescia Rosa Manenti Michela Brambilla Sandra Rosini Plasticità cerebrale Thanks for your attention